Progress on the Relationship between Ferroptosis and Cervical Cancer

doi:10.12280/gjszjk.20230120

Abstract

Abstract:

Ferroptosis as a new form of regulatory cell death is characterized by iron-dependent accumulation of lipid peroxides. Ferroptosis is regulated by many pathways, including glutathione peroxidase 4 (GPX4) pathway, iron metabolism and lipid metabolism pathway. Ferroptosis plays a key role in various physiological and pathological processes, such as tissue homeostasis, cancer and neurodegeneration. Cervical cancer is the fourth most common cancer among women in the world, with high mortality. Ferroptosis may be involved in the pathogenesis of cervical cancer, and that ferroptosis may be a potential therapeutic and prognostic target. Studies show that the inhibition of GPX4 and iron chelation, and the regulation of lipid metabolism pathway, can induce the ferroptosis of cervical cancer cells. In addition, some natural compounds and drugs have been proved to induce the ferroptosis of cervical cancer cells, indicating their potential as therapeutic agents for cervical cancer. Studying the mechanism and regulation of ferroptosis may provide new insights for the new treatment strategies of cervical cancer.

Key words: Uterine cervical neoplasms, Ferroptosis, Phospholipid hydroperoxide glutathione peroxidase, Glutathione, Reactive oxygen species, Therapy, Prognosis

GAO Ya-ting, MA Jian-hong, MA Yi-tong, LIU Chang. Progress on the Relationship between Ferroptosis and Cervical Cancer[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(5): 436-440.

Figures/Tables 1

References 28

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药物	机制	治疗方向
ACSL4	催化长链脂肪酸激活的关键酶，与多种生物反应密切相关，包括炎症反应、细胞死亡和免疫激活反应等	可以缩小宫颈癌癌灶体积，是肿瘤治疗的潜在靶点和生物标志物^[24]
OA	抑制肿瘤生长，增加肿瘤细胞Fe²⁺和ROS的积累，促进细胞铁死亡	OA作为ACSL4的天然激活剂，可增强其在宫颈癌中的抗癌作用^[25]
Nrf2	调节抗氧化应激信号通路，在多种癌症中通过激活铁代谢及GSH代谢相关基因和ROS解毒酶抑制铁死亡	脯氨酰异构酶1（prolyl isomerase 1）通过Nrf2/GPX4轴影响宫颈癌细胞的铁死亡和对铂类药物的敏感性，是宫颈癌的潜在治疗靶点^[26]
Cdc25	Cdc25/丙酮酸激酶M2/受体酪氨酸蛋白激酶ErbB-2（Cdc25/pyruvate kinase M2/receptor tyrosine-protein kinase ErbB-2，Cdc25/PKM2/ErbB2）轴抑制宫颈癌细胞铁死亡	通过抑制宫颈癌细胞铁死亡，增加癌细胞对放疗的抗性^[27]

药物	机制	治疗方向
ACSL4	催化长链脂肪酸激活的关键酶，与多种生物反应密切相关，包括炎症反应、细胞死亡和免疫激活反应等	可以缩小宫颈癌癌灶体积，是肿瘤治疗的潜在靶点和生物标志物^[24]
OA	抑制肿瘤生长，增加肿瘤细胞Fe²⁺和ROS的积累，促进细胞铁死亡	OA作为ACSL4的天然激活剂，可增强其在宫颈癌中的抗癌作用^[25]
Nrf2	调节抗氧化应激信号通路，在多种癌症中通过激活铁代谢及GSH代谢相关基因和ROS解毒酶抑制铁死亡	脯氨酰异构酶1（prolyl isomerase 1）通过Nrf2/GPX4轴影响宫颈癌细胞的铁死亡和对铂类药物的敏感性，是宫颈癌的潜在治疗靶点^[26]
Cdc25	Cdc25/丙酮酸激酶M2/受体酪氨酸蛋白激酶ErbB-2（Cdc25/pyruvate kinase M2/receptor tyrosine-protein kinase ErbB-2，Cdc25/PKM2/ErbB2）轴抑制宫颈癌细胞铁死亡	通过抑制宫颈癌细胞铁死亡，增加癌细胞对放疗的抗性^[27]